Biostable polyurethanes

ABSTRACT

The present invention relates to a biostable polyurethane or polyurea comprising: (a) a soft segment comprising a polysiloxane of the general formula (I); and (b) greater than O and less than 40 wt % of a hard segment which is a reaction product of a diisocyanate and a linear difunctional chain extender, processes for their preparation and their use in the manufacture of biomaterials, devices, articles or implants.

This application is a continuation application of U.S. patentapplication Ser. No. 14/216,190, filed Mar. 17, 2014, which is acontinuation application of U.S. patent application Ser. No. 12/225,753,filed Apr. 1, 2009, which application is a nationalization under 35U.S.C. 371 of PCT/AU2007/000409, filed Mar. 29, 2007 and published as WO2007/112485 A1, on Oct. 11, 2007, which claims priority under 35 U.S.C.119 to Australian Application No. 2006901675, filed Mar. 31, 2006; andwhich claims priority under 35 U.S.C. 119 (e) to U.S. Provisional PatentApplication Ser. No. 60/744,097, filed Mar. 31, 2006; which applicationsand publication are incorporated herein by reference and made a parthereof in their entirety.

The present invention relates to polyurethanes and processes for theirpreparation. The polyurethanes are biostable, creep resistant, acidresistant and abrasion resistant which makes them useful in themanufacture of biomaterials and medical devices, articles or implants,in particular long term implantable medical devices in the fields ofcardiology, orthopaedics, plastic surgery and gastroenterology.

BACKGROUND

The development of methodology to incorporate high silicone loadings inthe soft segment of polyurethanes has resulted in the production ofbiostable polyurethanes (Elast-Eon™). The soft segment of thesepolyurethanes is based on 80 wt % of a hydroxyl terminatedpolydimethylsiloxane (PDMS) and 20 wt % of a polyether polyolspecifically polyhexamethylene oxide (PHMO).

It was thought that the presence of the polyether was necessary in orderto act as a compatibiliser between. thermodynamically diverse moleculesof the isocyanate rich hard segment and the silicone rich soft segment.Polyurethanes with silicone contents higher than 80 wt % of the softsegment resulted in poorer mechanical properties which at that timeseemed to corroborate the compatibiliser theory.

The technology of Elast-Eon production has more recently evolved leadingto significant process breakthroughs that allow the incorporation ofhigher silicone content into the soft segment without a correspondingdecrease in mechanical properties.

A considerable amount of work has also been done in understanding thebiologically induced degradation mechanisms in polyurethanes. Oxidisingradicals emanating from foreign body giant cells (FBGC) in the vicinityof the implant are seen to be the major source of degradation ofpolyurethane based medical devices. As a result, it has been shown thatthe presence of oxidisable groups in polyurethanes are the primary sitesof the initiation of degradation. Therefore, a reduction in the contentof groups prone to oxidation will lead to an increase in the biologicalstability of the polyurethanes. As a consequence, it is now desirable tohave a soft segment which is based on PDMS instead of PDMS incombination with a polyether polyol.

SUMMARY

According to the present invention there is provided a biostablepolyurethane comprising:

(a) a soft segment comprising greater than 98 wt % of a polysiloxanehaving a molecular weight in the range of 500 to 1500 of the generalformula (I)

in which

A and A′ are O;

R₁, R₂ R₃ and R₄ are independently selected from C₁₋₆ alkyl;

R₅ and R₆ are independently selected from C₁₋₁₂ alkylene; and

p is an integer of 1 or greater, preferably 5 to 30, more preferably 8to 20; and

(b) greater than 0 and less than 40 wt % of a hard segment which is areaction product of a diisocyanate and a linear difunctional chainextender.

The present invention also provides a process for preparing thebiostable polyurethane defined above which comprises the steps of:

-   -   (i) reacting a hydroxy terminated polysiloxane of formula (I) as        defined above with a diisocyanate to form a prepolymer; and    -   (ii) high shear mixing the prepolymer of step (i) with a linear        difunctional chain extender.

Despite having a lower hard segment concentration, the polyurethanes ofthe present invention surprisingly possess an equivalent tensile modulusto the Elast-Eon polyurethanes in the range of 10 to 55 MPa. This isalso accompanied by biological stability and a 10 to 20% improvement increep resistance, acid resistance and abrasion resistance. Theseproperties make the polyurethanes useful in the manufacture ofbiomaterials and medical devices, articles or implants.

Thus, the present invention further provides a biomaterial, device,article or implant which is wholly or partly composed of the biostablepolyurethanes or polyurethane ureas as defined above.

DETAILED DESCRIPTION

The biostable polyurethanes of the present invention possess (a) a softsegment which comprises the polysiloxane of formula (I) defined aboveand (b) a hard segment which is the reaction product of a diisocyanateand a linear difunctional chain-extender. While in a preferredembodiment the soft segment only comprises the polysiloxane of formula(I), it will be appreciated that other soft segment components such aspolyether polyols or polycarbonate polyols may be present in an amountof up to 2 wt %, preferably up to 1 wt % based on the total amount ofsoft segment.

Suitable polyether polyols include those of formula (II):

in which

m is an integer of 2 or more, preferably 4 to 18; and

n is an integer of 2 to 50.

Polyether polyols of formula (II) wherein m is 4 or higher suchpolytetramethylene oxide (PTMO), polyhexamethylene oxide (PHMO),polyheptamethylene oxide, polyoctamethylene oxide (POMO) andpolydecamethylene oxide (PDMO) are preferred. The molecular weight rangeof the polyether polyol is preferably in the range of 200 to 5000, morepreferably 200 to 1200.

Suitable polycarbonate polyols include poly (alkylene carbonates) suchas poly(hexamethylene carbonate) and poly(decamethylene carbonate);polycarbonates prepared by reacting alkylene carbonate with alkanendiolfor example 1,4-butanediol, 1,10-decanediol (DD), 1,6-hexanediol (HD)and/or 2,2-diethyl 1,3-propanediol (DEPD); and silicon basedpolycarbonates prepared by reacting alkylene carbonate with1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethlyldisiloxane (BHTD) and/oralkanediols.

The soft and hard segments of polyurethanes typically phase separate andform separate domains. The hard segments organise to form ordered(crystalline) domains while the soft segments remain largely asamorphous domains and the two in combination are responsible for theexcellent mechanical properties of polyurethanes.

The amount of hard segment present in the polyurethanes of the presentinvention is greater than 0 and less than 40 wt %, preferably in therange of 10 to 39 wt %, more preferably between 25 to 37.5 wt %.

It is surprising that the tensile modulus of the polyurethanes of thepresent invention decreases as the amount of hard segment decreases.

It is observed that the tensile properties do not seem to be affectedsignificantly by the exclusion of the polyether from the soft segment.In particular, the tensile modulus actually shows an increase even withlower amounts of hard segment concentration. This is clearly a result ofenhanced phase separation that occurs with the polyurethanes of thepresent invention as opposed to the Elast-Eon polyurethanes. Theenhanced phase separation also shows up in improvements of properties ofcreep resistance, abrasion resistance and fatigue resistance.

A significant aspect of the exclusion of the polyether is the resultingimprovement in the oxidation resistance of the material. This ismeasured by subjecting the polyurethanes to a fixed time period test(28-72 days) in an oxidative solution containing high concentration ofoxidative radicals such as peroxides. The polyurethanes after the testare examined by various techniques including scanning electronmicroscopy (SEM) to assess and quantify the level of degradation. Thesetests are a good indicator of long term biological stability.Polyurethanes containing 100% polysiloxane in the soft segment showremarkable improvements in oxidative stability.

Similar improvements are noted in the resistance to acid degradationwith the 100% polysiloxane soft segment polyurethanes showingconsiderable improvement over the Elast-Eon polyurethanes having apolysiloxane polyether soft segment.

The amount of soft segment present in the polyurethane is at least 60 wt%, more preferably in the range of 60 wt % to 90 wt %, most preferably60 wt % to 75 wt %.

The high Si content results in polyurethanes which are biostable andshow improvements in mechanical properties and acid and abrasionresistance.

The NCO/OH or NRH ratio of the components of the polyurethanes arepreferably in the range of 0.97 to 1.03, more preferably 0.985 to 1.015.

Polysiloxane

The polysiloxane is of formula (I) defined above.

The term “C₁₋₆ alkyl” as used in formula (I) refers to straight chain,branched chain or cyclic hydrocarbon groups having from 1 to 6 carbonatoms, preferably 1 to 4 carbon atoms, more preferably methyl. Examplesinclude alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl, cyclopropyl,cyclobutyl, cyclopentyl and cyclohexyl.

The term “C₁₋₁₂ alkylene” refers to divalent straight chain, branchedchain or cyclic hydrocarbon groups having from 1 to 12 carbon atoms,preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms.Examples include ethylene, propylene, butylene, pentylene, hexylene,heptalene and octylene, dodecylene, cyclopropylene, cyclopentylene andcyclohexylene.

Preferred polysiloxanes are polysiloxane macrodiols which are hydroxyterminated polysiloxanes of formula (I).

A preferred polysiloxane is PDMS which is a polysiloxane of formula (I)wherein R₁ to R₄ are methyl and R₅ and R₆ are as defined above,preferably C₁₋₄ alkylene, more preferably ethylene or propylene.

The polysiloxane macrodiols may be prepared according to knownprocedures or obtained as commercially available products such asX-22-160AS from Shin Etsu in Japan which is a hydroxy terminatedpolysiloxane of formula (I) in which R₁ to R₄ are methyl, R₅ and R₆ areethylene, X is O and p is 8 to 20.

Other polysiloxanes are polysiloxane macrodiamines which are NHRterminated polysiloxanes of formula (I) in which R is as defined above,for example, amine terminated PDMS in which R is hydrogen, R₁ to R₄ aremethyl and R₅ and R₆ are as defined above, preferably C₁₋₆ alkylene,more preferably ethylene or propylene.

The molecular weight range of the polysiloxane is 500 to 1500.

It will be understood that the molecular weight values referred toherein are “number average molecular weights”.

The presence of an ether group increases the polarity of thepolysiloxane of formula (I) making it more amenable for reaction withthe diisocyanate. Polysiloxanes and diisocyanates are extremelyincompatible due to a large difference in their polarities. Any attemptto force a polymerisation between a diisocyanate and a silanol usuallyresults in polymers with poor mechanical properties and the need toemploy polymerisation conditions involving a solvent. The polarity ofthe polysiloxane of formula (I) assists in overcoming any prematurephase separation and maintaining good mechanical properties.

Diisocyanate

The diisocyanate may be an aliphatic, cyclic or aromatic diisocyanatessuch as, for example 4,4′-diphenylmethane diisocyanate (MDI), methylenebiscyclohexyl diisocyanate (H₁₂MDI), p-phenylene diisocyanate (p-PDI),trans-cyclohexane-1,4-diisocyanate (CHDI), 1,6-diisocyanatohexane(DICH), 1,5-diisocyanaton-aphthalene (NDI),para-tetramethylxylenediisocyanate (p-TMXDI), meta-tetramethylxylenediisocyanate (m-TMXDI), 2,4-toluene diisocyanate (2,4-TDI) isomers ormixtures thereof or isophorone diisocyanate (IPDI), Aromaticdiisocyanates such as MDI are preferred due their propensity to formuniform hard blocks that contribute both to good mechanical propertiesas well as biostability.

The amount of diisocyanate present is preferably in the range of 8 wt %to 35 wt %, more preferably 20 wt % to 35 wt % based on the total weightof the polyurethane.

Chain Extender

The term “difunctional linear chain extender” in the present contextmeans any chain extender having two functional groups per molecule suchas diols or diamines which are capable of reacting with an isocyanategroup. The functional group is attached to a primary functional carbonatom as opposed to a secondary functional carbon atom in the case of abranched chain extender.

The chain extender generally has a molecular weight range of 500 orless, preferably 15 to 500, more preferably 60 to 450.

The chain extender may be selected from diol or diamine chain extenders.

Examples of diol chain extenders include C₁₋₁₂ alkane diols such as1,4-butanediol (BDO), 1,6-hexanediol, 1,8-octanediol, 1,9-nonanediol,1,10-decanediol and 1,12-dodecanediol; cyclic diols such as1,4-cyclohexanediol, 1,4-cyclohexanedimethanol,1,4-bis(2-hydroxyethoxy)benzene and p-xyleneglycol; andsilicon-containing diols such as1,3-bis(4-hydroxybutyl)tetramethyldisiloxane and1,3-bis(6-hydroxyethoxypropyl)tetramethyldisiloxane. Preferably the diolchain extender is BDO.

Suitable diamine chain extenders include C₁₋₁₂ alkane diamines such as1,2-ethylenediamine, 1,3-propanediamine, 1,4-butanediamine and1,6-hexanediamine; and silicon-containing diamines such as1,3-bis(3-aminopropyl)tetramethyldisiloxane and1,3-bis(4-aminobutyl)tetramethyldisiloxane.

It is important that the chain extender be linear as the use of abranched chain extender would disrupt the morphology of the polyurethaneand result in poor biostability and reduced mechanical properties.

The amount of chain extender present is preferably in the range of 1 wt% to 5 wt %, more preferably wt % to 5 wt % based on the total weight ofthe polyurethane.

Process

The polyurethanes of the present invention are prepared by a two-stepbulk polymerisation procedure. The polymerisation can be carried out inconventional apparatus or within the confines of a reactive injectionmoulding or mixing machines.

In the two-step method, a prepolymer having terminally reactivepolyisocyanate groups is prepared by reacting a hydroxyl terminatedpolysiloxane of formula (I) with a diisocyanate. The prepolymer is thehigh shear mixed with a chain extender using any suitable knownapparatus such as a high shear and speed mixer for example a SilversonMixer. The high shear mixing ensures that the morphology of thepolyurethane is controlled so that there is proper distribution of thehard segment in the soft segment and to prevent premature phaseseparation. It is important to disperse evenly the chain extender intothe prepolymer. The high shear mixing ensures even distribution beforereaction. The polyurethane may then be cured by pouring the liquidpolyurethane into Teflon-coated trays and heated to about 100° C. Thecured slabs may then be granulated and melted through an extruder attemperatures of about 200° C. The melted polyurethane can then be passedthrough a strand die and the strands pelletised.

The process described above does not generally cause premature phaseseparation and yields polyurethanes that are compositionally homogeneousand transparent having high molecular weights. This process also has theadvantage of not requiring the use of any solvent to ensure that thesoft and hard segments are compatible during synthesis.

A further advantage of the incorporation of polysiloxane segments is therelative ease of processing of the polyurethane by conventional methodssuch as reactive injection moulding, rotational moulding, compressionmoulding and foaming without the need of added processing waxes. Ifdesired, however, conventional polyurethane processing additives such ascatalysts for example dibutyl tin dilaurate (DBTDL), stannous oxide(SO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DABU),1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane (DTDS),1,4-diaza-(2,2,2)-bicyclooctane (DABCO),N,N,N′,N′-tetramethylbutanediamine (TMBD) and dimethyltin dilaurate(DMTD); antioxidants for example Irganox (Registered Trade Mark);radical inhibitors for example trisnonylphenyl phosphite (TNPP);stabilisers; lubricants for example Irgawax (Registered Trade Mark);dyes; pigments; inorganic and/or organic fillers; and reinforcingmaterials can be incorporated into the polyurethane during preparation.Such additives are preferably added in step (i) of the process of thepresent invention.

Medical Applications

The polyurethanes of the present invention are particularly useful inpreparing biomaterials and medical devices, articles or implants as aconsequence of their biostability, creep resistance, acid resistance andabrasion resistance.

The term “biostable” refers to a stability when in contact with cellsand/or bodily fluids of living animals or humans.

The term “biomaterial” refers to a material which is used in situationswhere it comes into contact with the cells and/or bodily fluids ofliving animals or humans.

The medical devices, articles or implants may include catheters;stylets; bone suture anchors; vascular, oesophageal and bilial stents;cochlear implants; reconstructive facial surgery; controlled drugrelease devices; components in key hole surgery; biosensors; membranesfor cell encapsulations; medical guidewires; medical guidepins;cannularizations; pacemakers, defibrillators and neurostimulators andtheir respective electrode leads; ventricular assist devices;orthopaedic joints or parts thereof including spinal discs and smalljoints; cranioplasty plates; intraoccular lenses; urological stents andother urological devices; stent/graft devices; devicejoining/extending/repair sleeves; heart valves; vein grafts; vascularaccess ports; vascular shunts; blood purification devices; casts forbroken limbs; vein valve, angioplasty, electrophysiology and cardiacoutput catheters; plastic surgery implants such as breast implantshells; lapbands; gastric balloons; and tools and accessories forinsertion of medical devices, infusion and flow control devices.

It will be appreciated that polyurethanes having properties optimisedfor use in the construction of various medical devices, articles orimplants will also have other non-medical applications. Suchapplications may include toys and toy components, shape memory films,pipe couplings, electrical connectors, zero-insertion force connectors,Robotics, Aerospace actuators, dynamic displays, flow control devices,sporting goods and components thereof, body-conforming devices,temperature control devices, safety release devices and heat shrinkinsulation.

In the claims which follow and in the preceding description of theinvention, except where the context requires otherwise due to expresslanguage or necessary implication, the word “comprise” or variationssuch as “comprises” or “comprising” is used in an inclusive sense, i.e.to specify the presence of the stated features but not to preclude thepresence or addition of further features in various embodiments of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the Examples, reference will be made to the accompanying drawings inwhich:

FIG. 1 is a graph showing a comparison of the tensile and recovery (5MPa loading) between E2A and E2A modified;

FIG. 2 is a scanning electron micrograph (SEM) at 5000 timesmagnification for E2A after 24 days in vitro;

FIG. 3 is a SEM at 5000 times magnification for E2A modified after 24days in vitro;

FIG. 4 is a graph showing background corrected SAXS intensities as afunction of scattering vector: ▪ E2A and ▴ E2A modified; and

FIG. 5 is a graph showing (a) storage (E′) and (b) dissipation factor(tan d) as a function of temperature for Elast-Eon 2A. Untreatedmaterial (i) and oxidised sample (ii).

EXAMPLES

The invention will now be described with reference to the followingnon-limiting examples.

Example 1

This example illustrates the preparation and testing of an Elast-Eon 2A(E2A) formulation with 100% silicone in the soft segment.

Synthesis

PDMS (180.00 g, MW 958.15) was degassed at 80° C. for 24 h under vacuum(0.01 torr), the resultant moisture level was <150 parts per million.Molten MDI (1010.63 g, MW 250.00) was weighed into a three-neck roundbottom flask equipped with a mechanical stirrer, dropping funnel andnitrogen inlet. The flask was heated in an oil bath at 70° C. Thedegassed PDMS (2000 g) was then added through a dropping funnel over aperiod of 2 hours. The PDMS used in this example has the followingformula:

in which n is 8-20.

After the completion of PDMS addition, the reaction mixture was heatedfor a further 2 h with stirring under nitrogen at 80° C. The prepolymermixture was then degassed at 80° C. under vacuum (0.01 torr) for about 1h. The vacuum was released slowly under nitrogen atmosphere and 2810 gof the degassed prepolymer mixture was weighed into a tall drypolypropylene beaker and immediately placed in a nitrogen circulatingoven at 80° C. BDO (189.3 g, MW 90.00) was previously degassed over 24 hat 60° C. to moisture levels below 50 ppm. The overall stoichiometry wasmaintained at 1.015. BDO was added into the prepolymer mixture (2810 g)while using a highly dispersive, high shear and high speed mixer such asa Silverson Mixer. The mixture was stirred at high speed (6000 rpm) forabout 2 minutes. The polymer mixture was then poured into several Tefloncoated moulds and cured to a solid slab for 15 h in a nitrogencirculating oven at 100° C. After full cure the slabs were granulatedand extruded in a 25 mm diameter extruder, L/D ratio of 30/1 at a melttemperature of 200° C. The extrudate, in the form of cylindrical rods,was chopped into pellets suitable for further thermoplastic processing.

Tensile Testing

The pellets were compression moulded into 3 mm thick rectangular sheetsand samples were cut from these sheets that were subject to variousmechanical testing. Table 1 below shows the mechanical data comparisonbetween the two polyurethanes.

TABLE 1 Soft Segment Modulus of Tensile % Strain Tear Si CompositionElasticity strength at Strength Durometer Material Content % PDMS/PHMO(MPa) (MPa) break (kN/m) Hardness E2A 48 80/20 35 28 500 85 90A E2Amodified 60 100/0  56 27 560 84 90A

E2A is made with a soft segment that is a mix of 80 wt % of PDMS 1000and 20 wt % of PHMO. The ratio of the hard to soft segment in both E2Aand the modified version of E2A is 40/60. The hard segment comprises MDIand BDO. The tensile modulus increases with increased PDMS content butall the other properties are comparable.

Creep and Recovery

FIG. 1 is a graph providing a comparison of the tensile creepperformance of the polyurethanes. The polyurethanes were loaded to 60N(in about 10 sec), translating to a stress of approximately 5 MPa, andheld for 30 minutes. After 30 minutes the polyurethane was taken off theInstron and the gauge length was measured intermittently for 30 minutes.

A surprising improvement in creep and recovery performance is noted inthe polyurethane containing 100% silicone in the soft segment.

In-Vitro Accelerated Oxidative Ageing

Using the protocol described in E. M. Christenson, J. M. Anderson, A.Hiltner, Journal of Biomed. Mater. Res. A, 2004, 69, 407 in vitroaccelerated aging was performed at 37° C.±1° C. on unstrained filmsamples in an oxidative solution of 20% hydrogen peroxide in 0.1 Mcobalt chloride. The polyurethane films were treated for 24 days withthe change of solutions every 3 days in order to maintain a relativelyconstant concentration of radicals. Film samples were removed every 6days, washed thoroughly with water, vacuum dried before using forextraction experiments.

The SEMs at 5000 times magnification of the standard and the modifiedE2A are shown in FIGS. 2 and 3.

From the results it can be seen that the modified E2A performed evenbetter than standard E2A in terms of very low surface degradation. Thebiological stability that a 100% silicone content E2A provides issuperior to the standard E2A.

Example 2

This example illustrates the preparation and testing of E2A formulationswith 100% silicone in the soft segment and varying levels of hardsegment content.

Synthesis

The synthesis was exactly the same as that used in Example 1, but thelevels of the reactants were different as illustrated in Table 2 below.

TABLE 2 Hard Formulation Stoichiometry segment % MDI (g) PDMS (g) BDO(g) 1 1.015 35 910.3 1950 139.7 2 1.015 32.5 860.14 2025 114.86 3 1.01530 809.97 2100 90.03

These formulations were then compared with equivalent hard blockformulations made from a mixed macrodiol (80/20), PDMS/PHMO). Thecomparative tensile test results set out in Table 3 below.

TABLE 3 Modulus of Tensile Elasticity strength % Strain Tear StrengthDurometer Material Hard Segment % (MPa) (MPa) at break (kN/m) HardnessComparative 1 35 18.6 22.5 698 62.5 84A 1 35 21.0 23.1 711 67.1 86AComparative 2 32.5 12.7 21 676 56 78A 2 32.5 13 22.7 675 58 80AComparative 3 30 9.5 15.5 790 48.5 76A 3 30 10.0 20.2 799 52 73A

As can be seen in Table 3, the difference in the tensile modulusdecreases as the hard segment % decreases. This result is surprisingsince the difference in the modulus is high when the hard segmentcontent is 40%, as noted in Example 1. This was probably why theElast-Eon polyurethanes contain a compatibiliser in conjunction withsilicone in order to reduce the stiffness of the polyurethanes. However,the stiffness or modulus difference reduces dramatically as the overall% hard segment of the polyurethanes decreases.

Thus, Elast-Eon of equivalent modulus at lower hard segmentconcentration can be obtained with a soft segment composed entirely ofsilicone. This is accompanied by corresponding significant increase inbiological stability, creep resistance, acid resistance and abrasionresistance.

Example 3

This example illustrates the characterisation of the E2A and E2Amodified materials synthesised in Example 1.

Characterisation Methods

Dynamic mechanical analysis. The dynamic mechanical properties of thecopolymers were evaluated using a TA-Q800 DMA and a was Cooling (ModelCFL-50) for sub-ambient experiments. Film samples were tested in tensionfrom −120° C. to 150° C. at a heating rate of 3° C./min and frequency of1 Hz; the static force was preset at 1 N with a force track of 125%.

Small-angle X-ray scattering. SAXS data were collected on MolecularMetrology SAXS instrument consisting of a three-pinhole collimatedcamera [using a CuKα radiation source (λ=0.154 nm)] and atwo-dimensional multi-wire detector. The sample-to-detector distance was1.5 m.

The polyurethane films were cut into 1 cm×1 cm squares, which werestacked to a thickness of approximately 1 mm and secured by tape alongthe edges. The film stack was supported by placing it between two indexcards with a hole for the passage of the x-ray beam. The ensemble wasthen mounted onto sample holder provided by Molecular Metrology.

Absolute scattered intensities (in units of cm⁻¹) were determined bycalibration with a pre-calibrated cross-linked polyethylene (S-2907)secondary standard; this step is essential in order to obtainquantitative details on segment demixing. A silver behenate secondarystandard was used to calibrate the scattering vector.

Results

The results, as observed with the characterisation, indicate importantbehavioural aspects of the material.

The SAXS results in FIG. 4 show that the polyurethane made with onlyPDMS in the soft segment has a greater degree of phase separation thanthe polyurethane made with a blend of polyols, PDMS and PHMO. The dataare presented as I/I_(e)V, where I is the scattered intensity, I_(e) theintensity scattered by a single electron under identical conditions, andV the irradiated sample volume. The peak position (q_(max)) isindicative of the mean interdomain spacing, d, by d=2π/q_(max).

FIG. 5 shows the DMA plot of E2A before and after performing in vitrooxidative ageing. The glass transition temperature of the PDMS phase is˜−120° C. while that of the PHMO phase ˜20° C. Upon undergoingoxidation, the PDMS transition is unaffected while the PHMO transitionbroadens with a decrease in the tan d value and an increase in thestorage modulus. This shows that only the PHMO phase is affected onoxidation and is therefore the more susceptible part of the polymerstructure in terms of biostability.

It will be understood to persons skilled in the art of the inventionthat many modifications may be made without departing from the spiritand scope of the invention.

1.-21. (canceled)
 22. A biostable polyurethane urea comprising: (a)60-75 wt-% of a soft segment comprising greater than 98 wt-% of apolysiloxane having a molecular weight in the range of 500 to 1500 ofthe general formula (I)

in which A and A′ are N(C₁-C₆)alkyl or O; R₁, R₂ R₃ and R₄ areindependently selected from C₁₋ ₆ alkyl; R₅ and R₆ are independentlyselected from C₁₋₁₂ alkylene; and p is an integer of 1 or greater; (b)25-40 wt % of a hard segment which is a reaction product of 20-35 wt-%of a diisocyanate and 2-5 wt-% of a linear difunctional chain extender,based on the total weight of the polyurethane, wherein the lineardifunctional chain extender consists of a (C₁-C₁₂)alkane diol or aC₁-C₁₂ alkane diamine; and (c) wherein the soft segment comprises up toabout 2 wt-% of a polyether polyol, a polycarbonate polyol or acombination thereof.
 23. The polyurethane urea according to claim 22, inwhich the R₁ to R₄ in formula (I) are independently selected from C₁₋₄alkyl.
 24. The polyurethane urea according to claim 23, in which R₁ toR₄ in formula (I) are methyl.
 25. The polyurethane urea according toclaim 22, in which R₅ and R₆ in formula (I) are independently selectedfrom C₁₋₄ alkylene.
 26. The polyurethane urea according to claim 22, inwhich R₅ and R₆ in formula (I) are ethylene or propylene.
 27. Thepolyurethane urea according to claim 22, in which p in formula (i is aninteger of 5 to
 30. 28. The polyurethane urea according to claim 22, inwhich the diisocyanate is an aromatic diisocyanate.
 29. The polyurethaneurea according to claim 28, in which the aromatic diisocyanate is4,4′-diphenylmethyl diisocyanate (MDI).
 30. The polyurethane ureaaccording to claim 22, in which the chain extender has a molecularweight of 500 or less.
 31. The polyurethane urea according to claim 22,in which the C₁₋₁₂ alkane diol is 1,4-butanediol (BDO).
 32. A processfor preparing the biostable polyurethane urea according to claim 1 whichcomprises the steps of: (i) reacting the diisocyanate with the amine orhydroxy terminated polysiloxane of formula (I) according to claim 1 toform a prepolymer; and (ii) high shear mixing the prepolymer with thelinear difunctional chain extender.
 33. A biomaterial, device, articleor implant which is wholly or partly composed of the biostablepolyurethane urea according to claim
 22. 34. A biomaterial, device,article or implant according to claim 33 which is selected fromcatheters; stylets; bone suture anchors; vascular, oesophageal andbilial stents; cochlear implants; reconstructive facial surgery;controlled drug release devices; components in key hole surgery;biosensors; membranes for cell encapsulations; medical guidewires;medical guidepins; cannularizations; pacemakers, defibrillators andneurostimulators and their respective electrode leads; ventricularassist devices; orthopaedic joints or parts thereof; spinal discs andsmall joints; cranioplasty plates; intraoccular lenses; urologicalstents and other urological devices; stent/graft devices; devicejoining/extending/repair sleeves; heart valves; vein grafts; vascularaccess ports; vascular shunts; blood purification devices; casts forbroken limbs; vein valve, angioplasty, electrophysiology and cardiacoutput catheters; plastic surgery implants; breast implant shells;lapbands; gastric balloons; tools and accessories for insertion ofmedical devices, infusion and flow control devices; toys and toycomponents; shape memory films; pipe couplings; electrical connectors;zero-insertion force connectors; Robotics; Aerospace actuators; dynamicdisplays; flow control devices; sporting goods and components thereof;body-conforming devices; temperature control devices; safety releasedevices and heat shrink insulation.
 35. A polyurethane urea according toclaim 22, in which the amount of soft segment is 65-70 wt %.
 36. Thepolyurethane urea according to claim 22, in which p in formula (I) is aninteger of 8 to
 20. 37. The polyurethane urea according to claim 22, inwhich the chain extender has a molecular weight of 15 to
 500. 38. Thepolyurethane according to claim 22, in which the chain extender has amolecular weight of 60 to
 450. 39. The polyurethane of claim 22, whereinthe polyether polyol comprise those of the formula (II):

wherein m is an integer of 2 to 18; and n is an integer of 2 to
 50. 40.The polyurethane of claim 22, wherein the polycarbonate polyol comprisespoly(alkylene carbonates).
 41. The polyurethane of claim 40, wherein thepolycarbonate polyol comprises poly(hexamethylene carbonate andpoly(decamethylene carbonate).